Electrophilic fluorination of organic molecules with F2, or its derivatives is efficient, controllable and fast. F2 is a highly potent chemical agent. It is the most reactive pure element. (Bergman et al., Nucl. Med. Biol., 1997, vol. 24, pgs. 677-683). The fluorine atom is about the same size as the hydrogen atom. This makes it possible for fluorine to mimic hydrogen with respect to steric requirements in molecules as well as at binding sites on receptors and enzymes. Fluorine substitution can also have a profound effect on the lipofilicity and biological activity of small molecules. (Park et al., Drug Metab. Rev., 1994, vol. 26, pgs. 605-643). The Positron Emission Tomography technique makes it possible to follow, in a patient, the binding of radiolabeled ligands to receptor sites, thus making it possible to quantitate the number of binding sites in both healthy and diseased states. Displacement of the labeled ligands makes it possible to measure the affinity to the binding site. Tracer studies with potent and/or toxic neuroreceptor ligands require high specific radioactivity for the tracer, as the amount of mass that can be injected into a human subject is limited by the toxicity of the substance and its affinity for the receptor site. For an injected dose of typically 185 MBq, the amount will be 10 nmol when the specific radioactivity (“SA”) is 185 GBq/micromol. (Bergman et al.).
Electrophilic radiofluorine is particularly suitable for the synthesis of fluoroaryl compounds ([18F]Ar—F) by cleavage of aryl-metal bonds of typically Ar-MR (M=Sn, Hg, Si, R═(CH3)n) compounds either with [18F]F2 or [18F]CH3COOF. The factor limiting the more widespread use of the method has been the low specific radioactivity of the labeled fluorine gas available through radionuclide production from gas phase target materials, typically neon or 18O2 mixed with carrier F2. Gas targetry for the production of [18F]F2 has recently been extensively reported. Straatman et al. describe a method where n.c.a. [18F]HF, in an exchange reaction with F2, is converted to [18F]F2 by a microwave discharge. (Straatman et al., Label. Compd. Radiopharm., 1982, vol. 19, pg. 1373).
A simplistic way of producing 18F is to irradiate, with a particle accelerator beam, highly 18O-enriched water. Through the 18O(p,n) 18F nuclear reaction, up to several curies of radioactivity can be produced. The radiolabeled fluoride ([18F]F-aq) recovered after charged particle irradiation can be used for the production of numerous labeled neurotracers. (Bergman et al.) The synthetic chemistry, however, with this anion is usually neither simple nor fast, especially if more complex molecules are needed.
Furthermore, Bergman et al. developed a method for the routine use of [18F] F2 for synthesis of radiotracers for PET. The SA of the product should be such that studies with receptor ligands are possible. The SA of [18F]F2 achieved by Bergman et al. was about 90 GBq/micromole. Bergman et al. considered four different methods of excitation: a) excitation with a cyclotron particle beam; b) excitation with a hard UV-light; c) excitation via an electric discharge through a gas; and d) excitation with laser light. Methods b and c were considered to be practical, and were therefore tested by Bergman et al.
In view of the prior art, a more rapid method to mass produce [18F]F2 by obtaining a higher SA than previously reported is needed.
Discussion or citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.